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Association studies of ALOX5 and bone mineral density in healthy adults.

ABSTRACT: Animal studies suggest that arachidonate 5-lipoxygenase (encoded by ALOX5) may be a genetic determinant of bone mineral density. We tested this hypothesis in a sample of healthy men and women and did not find consistent evidence for an association between variation in this gene and either lumbar spine or femoral neck BMD.Phenotypic variation in bone mineral density (BMD) among healthy adults is influenced by both genetic and environmental factors. A recent mouse study implicated ALOX5, which encodes arachidonate 5-lipoxygenase, as a contributing factor to areal BMD (aBMD).Fifteen single nucleotide polymorphisms (SNPs) distributed throughout ALOX5 were genotyped in three healthy groups: 1,688 European American, premenopausal sisters, 512 African American premenopausal sisters and 715 European American brothers. Statistical analyses were performed in the three groups to test for association between these SNPs and femoral neck and lumbar spine aBMD.Significant (p < or = 0.05) evidence of association was observed with three of the SNPs. However, despite the linkage disequilibrium between SNPs, adjacent SNPs did not provide statistical evidence of association in any of the three study groups.These data do not provide consistent evidence of association between genomic variation in ALOX5 and clinical variability in aBMD in healthy subjects.

SUBMITTER: Foroud T

PROVIDER: S-EPMC2467476 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Association studies of ALOX5 and bone mineral density in healthy adults.

Foroud T T Ichikawa S S Koller D D Lai D D Curry L L Xuei X X Edenberg H J HJ Hui S S Peacock M M Econs M J MJ

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20071002 5

<h4>Unlabelled</h4>Animal studies suggest that arachidonate 5-lipoxygenase (encoded by ALOX5) may be a genetic determinant of bone mineral density. We tested this hypothesis in a sample of healthy men and women and did not find consistent evidence for an association between variation in this gene and either lumbar spine or femoral neck BMD.<h4>Introduction</h4>Phenotypic variation in bone mineral density (BMD) among healthy adults is influenced by both genetic and environmental factors. A recent ...[more]

PMID: 17909879

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Project description:UnlabelledThere is a paucity of normative bone mineral density (BMD) data in healthy African women. Baseline total hip and lumbar spine BMD was measured in premenopausal women. BMD distribution was comparable to that of a reference population and was impacted by several factors including contraception and duration of lactation.IntroductionNormative data on bone mineral density (BMD) and the cumulative impact of lactation, contraceptive use, and other factors on BMD in healthy African women have not been well studied.ObjectivesThe objective of this study was to determine the factors associated with BMD in healthy premenopausal women in Uganda and Zimbabwe.MethodsBaseline total hip (TH) and lumbar spine (LS) BMD was measured by dual x-ray absorptiometry in 518 healthy, premenopausal black women enrolling in VOICE, an HIV-1 chemoprevention trial, at sites in Uganda and Zimbabwe. Contraceptive and lactation histories, physical activity assessment, calcium intake, and serum vitamin D levels were assessed. Independent factors associated with BMD were identified using an analysis of covariance model.ResultsThe study enrolled 331 women from Zimbabwe and 187 women from Uganda. Median age was 29 years (IQR 25, 32) and median body mass index (BMI) was 24.8 kg/m(2) (IQR 22.2, 28.6). In univariate analyses, lower TH BMD values were associated with residence in Uganda (p < 0.001), lower BMI (p < 0.001), and any use of and duration of depot-medroxyprogresterone acetate. Use of oral contraceptives, progestin-only implants, and higher physical activity levels were protective against reduced BMD. Similarly, lower LS BMD values were associated with these same factors but also higher parity and history of breastfeeding. In a multivariable analysis, lower TH and LS BMD values were associated with enrollment in Uganda, lower BMI, and lower physical activity level; contraceptive use was associated with lower spine BMD, and breastfeeding contributed to lower total hip BMD.ConclusionsAmong healthy premenopausal women, TH and LS BMD was higher in Zimbabwe than Uganda. Additional factors independently associated with BMD included BMI, physical activity level, contraceptive use, and lactation.

Project description:BACKGROUND:Growing evidence indicates that homocysteine is a noteworthy marker for general health status. However, research regarding plasma total homocysteine (tHcy) levels and bone mineral density (BMD) is sparse and controversial. Hence, we aimed to investigate the association between plasma tHcy level within normal range and lumbar BMD in adults. METHODS:In this cross-sectional study, using the National Health and Nutrition Examination Survey database, data on 10748 adults aged between 30 and 85?years were analyzed. The weighted multiple logistic regression analyses were conducted to evaluate the association between plasma tHcy level and lumbar BMD. The fitted smoothing curves were performed to explore potential non-linear relationships. When non-linearity was detected, we further calculated the inflection point using a recursive algorithm and constructed a weighted two-piecewise linear regression model. RESULTS:After adjusting for all the covariates, the association between plasma tHcy and lumbar BMD was different in various age groups (adults aged 30-49?years: ? = -0.0004, 95% CI -0.0025, 0.0018; adults aged 50-69?years: ? = 0.0001, 95% CI -0.0025, 0.0026; adults aged 70-85?years: ? = 0.0050, 95% CI 0.0008, 0.0092). In the subgroup analysis stratified by gender, this association also differed based on gender. There was a negative trend in females (aged 30-49?years: ? = -0.0022, 95% CI -0.0054, 0.0011; aged 50-69?years: ? = -0.0028, 95% CI -0.0062, 0.0007), and a positive trend in males (aged 30-49?years: ? = 0.0018, 95% CI -0.0012, 0.0048; aged 50-69?years: ? = 0.0027, 95% CI -0.0009, 0.0063) in both 30-49?years group and 50-69?years group. In the 70-85?years group, this association was significantly positive in males (? = 0.0136, 95% CI 0.0068, 0.0204), but was not significantly different in females (? = 0.0007, 95% CI -0.0046, 0.0060). CONCLUSION:The correlation between plasma tHcy level within the normal range and lumbar BMD differs by age and gender.

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Association studies of ALOX5 and bone mineral density in healthy adults.

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Association studies of ALOX5 and bone mineral density in healthy adults.

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